Table 3.
Characteristics of antiviral drugs approved for cytomegalovirus
| Drug Name | Ganciclovir and valganciclovir | Foscarnet | Cidofovir | Letermovir |
|---|---|---|---|---|
| Mechanism of action | 2ʹ-deoxyguanosine analogue Competitive binding to UL54 DNA polymerase Needs phosphorylation by CMV (UL97 encoded) and host kinases Virostatic agent |
Pyrophosphate analogue Noncompetitive inhibitor of many RNA and DNA polymerases (UL54 DNA polymerase in CMV) Virostatic agent |
Acyclic monophosphate deoxycytidine analogue Competitive substrate of UL54 DNA polymerase leads to inhibition of viral DNA synthesis through incorporation into growing viral DNA chain Virostatic agent |
Inhibits viral terminase complex, encoded by genes UL56, UL51 and UL89 Virostatic agent |
| Indications/uses | CMV retinitis CMV prophylaxis SOT Non-FDA uses: CMV disease CMV preemptive strategy CMV prophylaxis in HSCT |
CMV retinitis Non-FDA uses: second line for GCV resistant CMV disease therapy, prophylaxis or preemptive therapy |
CMV retinitis Non-FDA uses: 2nd line for GCV resistant CMV disease therapy, prophylaxis or preemptive therapy |
CMV prophylaxis in CMV-seropositive HSCT recipients |
| Formulations | GCV IV only VGCV oral |
IV only | IV only Lipid conjugate not yet approved (brincidofovir) |
IV and PO |
| Adverse effects | Pancytopenia and myelosuppression (leukopenia/neutropenia++) Renal injury Diarrhea Less common: pruritus, nausea, fever, torsade de pointe |
Renal injury Electrolytes wasting Neutropenia Less common: headache, diarrhea, fever, QTc prolongation |
Renal injury Proteinuria Neutropenia Ocular toxicity (iritis, uveitis, amblyopia) Less common: headaches, shivering, rash, alopecia, dyspnea |
Uncommon, mainly GI (gastritis, nausea), dyspnea, hepatitis |
| Resistance mechanism | Mutations in UL97 gene prevent activation of drug Mutations in UL54 gene prevent binding to DNA polymerase (may confer cross-resistance with all DNA-polymerase active antivirals) |
Mutations in UL54 gene prevent binding to DNA polymerase (may confer cross-resistance with all DNA-polymerase active antivirals) | Mutations in UL54 gene prevent binding to DNA polymerase (may confer cross-resistance with all DNA-polymerase active antivirals) | Mutations in UL56 gene Less commonly, mutations in UL51 or UL89 genes |
Abbreviations: CMV, cytomegalovirus; GVC, Ganciclovir; HSCT, hematopoietic stem cell transplant; IV, intravenous; PO, oral; GI, gastrointestinal; VGCV, Valganciclovir.